Overexpression of CREPT confers colorectal cancer sensitivity to fluorouracil

World J Gastroenterol. 2018 Jan 28;24(4):475-483. doi: 10.3748/wjg.v24.i4.475.

Abstract

Aim: To investigate expression of cell cycle-related and expression-elevated protein in tumor (CREPT) in colorectal cancer (CRC) and determine its prognostic value in response to 5-fluorouracil (5-FU).

Methods: The relative expression of CREPT in CRC tumor samples was determined using immunohistochemistry. The protein content in cell lines was analyzed by immunoblotting. Cell viability was measured with the CCK-8 assay. Cell cycle and apoptosis analyses were performed with flow cytometry.

Results: CREPT was overexpressed in CRC tissues and correlated with histological grade. Clinicopathological analysis indicated that CREPT was positively related to tumor progression. Exogenous expression of CREPT stimulated cell proliferation and accelerated the cell cycle. More importantly, high expression of CREPT sensitized CRC cells to 5-FU treatment. Furthermore, we demonstrated that 5-FU elicited significant apoptosis in CREPT-positive cells.

Conclusion: Aberrant overexpression of CREPT contributes to tumorigenesis of CRC by promoting cell proliferation and accelerating the cell cycle, and confers sensitivity to 5-FU. CREPT is a potential prognostic biomarker for 5-FU in CRC.

Keywords: 5-Fluorouracil; Apoptosis; CREPT; Cell proliferation; Colorectal cancer.

MeSH terms

  • Adenoma / drug therapy
  • Adenoma / mortality
  • Adenoma / pathology*
  • Antimetabolites, Antineoplastic / pharmacology
  • Antimetabolites, Antineoplastic / therapeutic use*
  • Apoptosis / drug effects
  • Biomarkers, Tumor / metabolism*
  • Carcinogenesis
  • Cell Cycle
  • Cell Cycle Proteins / metabolism*
  • Cell Line, Tumor
  • Cell Proliferation
  • Cell Survival / drug effects
  • Colorectal Neoplasms / drug therapy
  • Colorectal Neoplasms / mortality
  • Colorectal Neoplasms / pathology*
  • Disease Progression
  • Drug Resistance, Neoplasm
  • Flow Cytometry
  • Fluorouracil / pharmacology
  • Fluorouracil / therapeutic use*
  • Humans
  • Neoplasm Grading
  • Neoplasm Proteins / metabolism*
  • Prognosis
  • Survival Analysis
  • Up-Regulation

Substances

  • Antimetabolites, Antineoplastic
  • Biomarkers, Tumor
  • Cell Cycle Proteins
  • Neoplasm Proteins
  • RPRD1B protein, human
  • Fluorouracil